Genomics Flashcards
monogenic diseases
single gene defect e.g. CF
polygenic disases
combination of genetics and environment
- not guaranteed to inherit
how do we know which genes are involved in disease
GWAS
GWAS
looks for SNPs which are over expressed in diseased patients
SNPs do not have to be
coding for a gene- can act as a merger for mutations in regulatory regions
for GWAS to be useful
we have to know what all genes are responsible for
what can we use to find out what genes do
CRISPr- knock out the gene and see what effect it has
if SNPs are significantly moe common than you would expect
then you can suspect a nearby gene is involved
GWAS and case control
1) take 1000s of controls and patients
2) use GWAS to maps SNPs
3) look for over representation of SNP in patients
bigger sample size will
identify smaller effects
-can detect contribution of a variant of a few percent e.g. if you have this SNP, your chance of developing the disease increased by a tiny amount
SNPs and drug development
often get several genes identified which are involved in shared pathway
- gives clue to disease mechanism
- good drug target
prospective cohort and GWAS
-volunteers donate their genome- all sorts of variables measured over the years e.g. weight, blood count, diseases developed
GWAS cannot
explain all common disease - environment must be important
e.g. smoking and lung cancer
epigenetic changes
changes to the DNA which do not affect its base sequence. thought to be environmental e.g. methylation switches off and acetylation switches on
epigenetic changes are thought to be
environmental
genetic linkage
a measure of how resistance to recombination a genetic marker and phenotype are
many affected patients with genetic linkage have
codon deletions
often just ….. sequenced in GWAS
exomes
trio analysis
how to find out what condition someone is suffering with and what gene is causing it
how does trio analysis work
1) sequence DNA of both parents
2) sequence DNA of child (diseased)
3) look for de novo changes
de novo changes
may be genes responsible for the disease
only …… are sequenced in trio analysis
exomes
RNA sequencing can be used to
quantify gene expression in different types of cells e.g. normoxic and hypoxic
GWAS is an example of
hypothesis free research
personalised therapies
e.g. if doctors know your genes, and the specific mutation which is causing your cancer e.g. RAS , then they could design a drug which targets RAS activity and this would mean that therapies were directly targeting the cause of the problem
genetic info can also be used yo
predict right dosage to reduce side effect
example of personalised medicine
some breast cancer drugs only work in women with particular genetic variation. If testing shows patients with advanced melanoma had e a certain variation, 2 new approved drugs can treat them
